1. Field of the Invention
The invention relates to the field of topical antimicrobial wash and carrier solutions. The solutions disclosed herein are substantially non-irritating and thus, are especially suited to deliver topically pharmaceutical active agents, to clean and/or treat wounds or tissues.
2. Description of the Related Art
A variety of antimicrobial wash and carrier solutions are currently used to wash skin or other tissue surfaces, including wounds, to remove dirt, debris, or to loosen or soften crusted lymph or blood clots. In some instances, such solutions are used to disinfect a tissue and thus, curb or prevent an infection. In addition, such solutions can be used as carriers for pharmaceutically active agents to be topically applied to a given tissue.
Under normal circumstances (i.e., in the absence of heightened pain sensitivity) a wash solution should preferably be non-irritating. The tissues treated with wash solutions are often inflamed and thus, have a heightened sensitivity to pain, compelling the use of non-irritating substances. Unfortunately, a great number of wash solutions presently available elicit tissue irritation, making their use in the pediatric and veterinary setting cumbersome. For the most part, non-specific disinfectant/antimicrobial solutions (e.g., solutions including acetic acid) described in the art may actually cause or exacerbate tissue irritation at the site of use because of their nature and/or effective concentration or treatment time required.
Solutions, which differ from normal serum in tonicity, have been shown to cause pain on injection, electrolyte shifts, or even tissue irritation following contact. This effect depends on the degree of deviation from isotonicity. For example, ophthalmic preparations for instillation in the eye should be isotonic in nature to avoid irritation. Therefore, wash solutions should be isotonic in nature to avoid exacerbation of irritation associated with tissue damage (see e.g., Remington: The Science and Practice of Pharmacy, 19th Ed., Ch. 36, Gennaro, A. R., Ed, Mack Publishing Co. (1995)).
Wash solutions have been used as carrier solutions by supplementing them, for example, with one or more antibiotic(s). Moreover, combinations of Tris-EDTA solutions with specific antibiotics have been postulated to have a synergistic effect against a variety of infectious agents and have been described extensively in the literature at least as early as 1974 (see for example Blue et al. (1974), Wooley et al. (1983), Farca et al. (1997), see also PCT/US01/29133 describing various formulations for the treatment of specific Gram positive and Gram negative bacterial infections using Tris-EDTA, a variety of antibiotics, and a carrier). However, quite often the effectiveness of this well-known approach is hampered by the development of microbial antibiotic resistance.
An ideal wash/carrier solution should also be a non-specific broad-spectrum antimicrobial for initial use until the specific infection is identified, and subsequently as a carrier (e.g., for antibiotics). Non-specific broad-spectrum antimicrobial properties are useful (a) to aid in cleansing and treating the underlying tissue (e.g., to treat an existing infection or prevent an infection); and (b) to minimize and preferably even prevent the occurrence of back contamination of a multi-dose dispenser, thereby minimizing inadvertent cross-contamination from use to use and/or from user to user.
Several solutions described in the literature include a rather harsh disinfecting agent such as boric acid which are known to be toxic (boric acid has been removed from many hospitals after reports showed that repeated applications to damaged tissues resulted in the absorption of boric acid in sufficient amounts to cause acute poisoning causing death in half of the patients accidentally intoxicated (Goodman and Gilman's The Pharmacological Basis of Therapeutics, 5th Ed., Ch. 50, page 994, McGraw Hill Companies Inc., New York (1975).). To exemplify, U.S. Pat. No. 5,480,658 describes a “pH balanced”—e.g., alkaline pH—multi-purpose cleaning solution containing acetic acid and boric acid in a water base for the routine cleaning of the ear, the prevention and treatment of ear disease such as “swimmer's ear,” and wound cleaning. Similarly, U.S. Pat. No. 5,853,767 discloses a solution comprising, as active ingredients, both acetic acid and boric acid for the treatment of bacterial and fungal skin infections. The solution is described as having bacteriostatic, bacteriocidal and anti-fungal properties, and as useful for the treatment of vaginal infections, such as vaginitis.
The alkaline pH is useful for conditioning and softening biological tissues, and increasing the penetration of pharmaceutical agents. The exudates associated with infected lesions are acidic in nature and can inactivate or reduce the efficacy of many commonly used antibiotic agents. An alkaline pH wash solution can aid in the neutralization of the acidic environment of the lesion thereby allowing for increased efficacy for the commonly used antibiotic agents. Unfortunately, several solutions described to date are acidic. U.S. Pat. No. 5,631,218 is to a disinfecting solution including an ortho-hydroxy benzoic acid derivative (e.g., salicylic acid) and an amphoteric surfactant and/or an alkoxylated alcohol nonionic surfactant (e.g., an ethoxylated alcohol). The solution has a pH of 1.0-5.5. Similarly, U.S. Pat. No. 6,214,363 discloses a rinse-off antimicrobial cleansing composition including an antimicrobial agent, an anionic surfactant, a proton donating agent, and a deposition aid in water, in which the composition is adjusted to a pH of from about 3.0 to about 6.0.
Other solutions described in the art include U.S. Pat. No. 6,211,238 disclosing anionic surfactants that are used in conjunction with an antifungal acid and a chelating agent to preserve topically administrable pharmaceutical compositions without the need for a conventional preservative, such as benzalkonium chloride. U.S. Pat. No. 6,284,749 discloses a preservative system for topically administrable pharmaceutical compositions including fatty acid/amino acid soaps in conjunction with an antifungal acid and a chelating agent.
Thus, there is a need for wash and carrier solutions overcoming the shortcomings of presently available solutions. Such wash and carrier solutions ideally should be non-toxic, non-irritating, isotonic, possess non-specific broad-spectrum antimicrobial properties, and have an alkaline pH.